Pre-stimulus Activity Mediates Event-Related Theta Synchronization and Alpha Desynchronization During Memory Formation in Healthy Aging

Abstract

The capacity to learn is a key determinant for the quality of life but is known to decline to varying degrees with age. However, despite mounting evidence of memory deficits in older age, the neural mechanisms contributing to successful or impeded memory remain unclear. Previous research has primarily focused on memory formation through remembered versus forgotten comparisons, lacking the ability to capture the incremental nature of learning. Moreover, previous EEG studies have primarily examined oscillatory brain activity during the encoding phase, such as event-related synchronization (ERS) of mid-frontal theta and desynchronisation (ERD) of parietal alpha, while neglecting the potential influence of pre-stimulus activity. To address these limitations, we employed a sequence learning paradigm, where 113 young and 117 older participants learned a fixed sequence of visual locations through repeated observations (6423 sequence repetitions, 55 944 stimuli). This paradigm enabled us to investigate mid-frontal theta ERS, parietal alpha ERD, and how they are affected by pre-stimulus activity during the incremental learning process. Behavioral results revealed that young subjects learned significantly faster than older subjects, in line with expected age-related cognitive decline. Successful incremental learning was directly linked to decreases of mid-frontal theta ERS and increases of parietal alpha ERD. Notably, these neurophysiological changes were less pronounced in older individuals, reflecting a slower rate of learning. Importantly, the mediation analysis revealed that in both age groups, mid-frontal pre-stimulus theta partially mediated the relationship between learning and mid-frontal theta ERS. Furthermore, the overall impact of learning on parietal alpha ERD was primarily driven by its positive influence on pre-stimulus alpha activity. Our findings offer new insights into the age-related differences in memory formation and highlight the importance of pre-stimulus activity in explaining post-stimulus responses during learning.